Section 3. Current status of downstaging of hepatocellular carcinoma before liver transplantation.

Abstract

Liver transplantation (LT) is a well-established option of cure for hepatocellular carcinoma (HCC). Milan criteria is recognized as standard for selection of patients and set the baseline of survival to be achieved. It has been shown that tumor biology including differentiation, vascular invasion, and serum α-fetoprotein (AFP) predict posttransplant recurrence and survival better than morphology. Downstaging by locoregional therapies of HCC before LT, with the response to treatments and progression within observation period, serves as a selection tool rather than modulation of tumor biology. It selects those patients outside standard criteria at presentation but good tumor biology and high chance of good outcome to receive transplantation. The definition of downstaging should be differentiated from neo-adjuvant therapy, and the objectives in surgical and pretransplant candidates also differ.Published studies in this area showed variation in inclusion criteria, downstaging protocol and assessment of successful downstaging. Tumor biology predownstaging and postdownstaging was not incorporated. Posttransplant outcome were not clearly stated with regard to intention-to-treat survival, disease-free survival, and comparison against those originally within criteria. Meta-analysis of these results was impossible. Nevertheless, majority had reasonable protocol and were able to select patients whom likely to have good outcome. At present, there is no evidence that downstaged patients have a poorer prognosis than those presenting within the Milan criteria. Patients with tumors outside Milan criteria should be offered downstaging therapies. Those who are successfully downstaged to within Milan criteria should be eligible to liver transplant as same as those initially fit the criteria. In the last decade, various extended criteria of HCC for LT have been proposed and reported satisfactory survival. That makes downstaging technically unnecessary.To refine and validate the role of downstaging, it needs collaborative and prospective study with significant sample size, adequate preoperative staging, standardized protocol of selection of patients, and approaches to downstaging. Selection criteria should include histopathological data on tumor biology and serum AFP. There should be standardized definition of successful downstaging. Posttransplant disease-free survival should be reported in detail and compared with those who fit the standard criteria initially. A consistent immunosuppressant protocol is important to avoid bias.